1. Field of the Invention
The present invention relates to cancer detection. More specifically, the present invention discloses an efficient method for identifying important cancer biomarkers and identifying cancer progression using loss of pro-u-PA in urine as a marker of more advanced carcinoma.
2. Description of the Prior Art
Transitional cell carcinoma of the bladder is the second most common malignancy of the genitourinary tract and the second most common cause of death from genitourinary tumors. Depending on the depth of muscle invasion, bladder cancers tend to occur in two principal forms: low-grade superficial tumors and high-grade invasive cancer. Superficial bladder cancer accounts for approximately 70% to 80% of all newly diagnosed bladder cancers. Because of the multifocal nature of urothelial cancers, patients who survive bladder cancer remain at risk of invasive disease. Most invasive tumors are nodular, metastatic during the early phase, and have poor prognosis.
The major problem with bladder cancers is the high recurrence rate of superficial cancers: more than half of superficial tumors recur within 5 years and 10-20% of these progress to invasive disease. It is thus important to detect the early recurrence of superficial cancer before the cells undergo changes that lead to invasive phenotype. Clinical and histo-pathological factors that might assist in the prediction of tumor recurrence and the progression of bladder cancer have been studied. These parameters, when used with the TNM system, will serve as useful and specific tools to provide crucial information about the response to treatment and prognosis of cancer. An ideal prognostic factor must be of sufficient sensitivity and specificity so as to allow treatment decisions on a case-by-case basis. Cytologic analysis of voided urine is the most commonly used noninvasive method for detecting transitional cell carcinoma, but its utility is severely constrained by its low sensitivity. Several potential diagnostic markers for bladder cancer have been identified, including nuclear matrix protein 22, bladder tumor antigen, and telomerase. Although analysis of these markers allows a more sensitive detection of bladder cancer than urine cytology, their use is limited by low specificity.
On the other hand, specific genetic alterations have been implicated in the molecular pathogenesis of transitional cell carcinoma, with mutations reported in the cell cycle regulatory genes, oncogenes, and tumor suppressor genes. However, it has proven difficult to use these genetic alterations as diagnostic markers of bladder cancer because of their low sensitivity.
Therefore there is need for an improved noninvasive method for finding markers of bladder cancer and for efficiently detecting cancer progression.